{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T21:07:24Z","timestamp":1774472844617,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T00:00:00Z","timestamp":1567468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consejer\u00eda de Salud de Andaluc\u00eda","award":["PS-0305-2016"],"award-info":[{"award-number":["PS-0305-2016"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Identifying newborns at risk for cystic fibrosis (CF) by newborn screening (NBS) using dried blood spot (DBS) specimens provides an opportunity for presymptomatic detection. All NBS strategies for CF begin with measuring immunoreactive trypsinogen (IRT). Pancreatitis-associated protein (PAP) has been suggested as second-tier testing. The main objective of this study was to evaluate the analytical performance of an IRT\/PAP\/IRT strategy versus the current IRT\/IRT strategy over a two-year pilot study including 68,502 newborns. The design of the study, carried out in a prospective and parallel manner, allowed us to compare four different CF-NBS protocols after performing a post hoc analysis. The best PAP cutoff point and the potential sources of PAP false positive results in our non-CF newborn population were also studied. 14 CF newborns were detected, resulting in an overall CF prevalence of 1\/4, 893 newborns. The IRT\/IRT algorithm detected all CF cases, but the IRT\/PAP\/IRT algorithm failed to detect one case of CF. The IRT\/PAP\/IRT with an IRT-dependent safety net protocol was a good alternative to improve sensitivity to 100%. The IRT \u00d7 PAP\/IRT strategy clearly performed better, with a sensitivity of 100% and a positive predictive value (PPV) of 39%. Our calculated optimal cutoffs were 2.31 \u00b5g\/L for PAP and 167.4 \u00b5g2\/L2 for IRT \u00d7 PAP. PAP levels were higher in females and newborns with low birth weight. PAP false positive results were found mainly in newborns with conditions such as prematurity, sepsis, and hypoxic-ischemic encephalopathy.<\/jats:p>","DOI":"10.3390\/ijns5030032","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T08:28:13Z","timestamp":1567585693000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Initial Evaluation of Prospective and Parallel Assessments of Cystic Fibrosis Newborn Screening Protocols in Eastern Andalusia: IRT\/IRT versus IRT\/PAP\/IRT"],"prefix":"10.3390","volume":"5","author":[{"given":"Ilham","family":"Sadik","sequence":"first","affiliation":[{"name":"Clinical Laboratory, Hospital La L\u00ednea de la Concepci\u00f3n, 11300 C\u00e1diz, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inmaculada","family":"P\u00e9rez de Algaba","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, M\u00e1laga Regional University Hospital, Avenida Arroyo de los Angeles s\/n, 29011 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo","family":"Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, M\u00e1laga Regional University Hospital, Avenida Arroyo de los Angeles s\/n, 29011 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Benito","sequence":"additional","affiliation":[{"name":"Department of Genetics, M\u00e1laga Regional University Hospital, 29011 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-3747","authenticated-orcid":false,"given":"Javier","family":"Blasco-Alonso","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, M\u00e1laga Regional University Hospital, 29011 M\u00e1laga, Spain"},{"name":"Institute of Biomedical Research in M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pilar","family":"Caro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, M\u00e1laga Regional University Hospital, 29011 M\u00e1laga, Spain"},{"name":"Institute of Biomedical Research in M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"Department of Pharmacology and Pediatrics, University of M\u00e1laga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3004-252X","authenticated-orcid":false,"given":"V\u00edctor M.","family":"Navas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, M\u00e1laga Regional University Hospital, 29011 M\u00e1laga, Spain"},{"name":"Institute of Biomedical Research in M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5515-3034","authenticated-orcid":false,"given":"Javier","family":"P\u00e9rez-Fr\u00edas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, M\u00e1laga Regional University Hospital, 29011 M\u00e1laga, Spain"},{"name":"Institute of Biomedical Research in M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"Department of Pharmacology and Pediatrics, University of M\u00e1laga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estela","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, M\u00e1laga Regional University Hospital, 29011 M\u00e1laga, Spain"},{"name":"Institute of Biomedical Research in M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"},{"name":"Department of Pharmacology and Pediatrics, University of M\u00e1laga, 29071 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, M\u00e1laga Regional University Hospital, 29011 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-1563","authenticated-orcid":false,"given":"Raquel","family":"Yahyaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders and Newborn Screening Center of Eastern Andalusia, M\u00e1laga Regional University Hospital, Avenida Arroyo de los Angeles s\/n, 29011 M\u00e1laga, Spain"},{"name":"Institute of Biomedical Research in M\u00e1laga-IBIMA, 29010 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1146\/annurev.ge.29.120195.004021","article-title":"Cystic fibrosis: Genotypic and phenotypic variations","volume":"29","author":"Zielenski","year":"1995","journal-title":"Annu. 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